Background: The economic implications of dialysis-requiring allograft dysfunction early after kidney transplantation are not well-described. Methods: Data for Medicare-insured adult kidney transplant recipients in 1995-2004 who did not develop permanent graft failure in the first 90 days were drawn from the United States Renal Data System. We identified dialysis treatmentrecords from Medicare claims and categorized patients according to frequency and duration of posttransplant dialysis as: first week (delayed graft function, DGF), second week, weeks 3 or 4, second month, or third month.Associations of dialysis requirements withMedicare payments for the transplant hospitalization and over the next three years were estimated with multivariable linear regression. Graft and patient survival according to early dialysis requirements were examined with multivariable survival analysis. Results: Among 37,533 recipients, 15,314 (41%) experienced DGF and 3,184 (21% of those with DGF) received dialysis beyond the first week. Compared with no dialysis in the first 3 months, adjusted marginal first-yearcosts associated with early post-transplant dialysis ranged from $6,467 for dialysis requirement limited to first week to $27,606 for dialysis in multiple periods (p<0.0001). Patients who experienced DGF and received dialysis in >2 early periods were more than twice as likely to lose their grafts within 3 years as those without early dialysis requirements. Conclusions: While dialysis in the first week post-transplant is an adverse risk marker, early dialysis in weeks 2 to 12 is associated with similarly adverse, if not worse, costs and clinical consequences. This observation supports a need for broader definition of DGF.

Objective: Chronic allograft nephropathy (CAN) is common following renal transplantation in cats and people. Aldosterone potentiates ongoing renal injury; however its role in CAN is less defined. Spironolactone, an aldosterone receptor blocker, is protective in other rodent models of renal injury. The purpose of this study was to evaluate spironolactone on the development of CAN in a rat model
Animals: Fisher and Lewis, adult, male rats.
Procedures: A Lewis to Fisher model of CAN was used. Rats were divided into 4 groups, 2 nephrectomy controls (CON) and 2 transplantation (TX) groups. Two groups (a CON and TX) received tap water (0.25 ml/day orally), and the remaining 2 received spironolactone (10 mg/kg orally) daily for 16 weeks post transplantation. Serum creatinine concentration, urine-protein: urine-creatinine (UP: UC), and changes in renal cortex gene expression were measured during and at 16 weeks after transplantation.
Results: There were no significant differences in any of the outcome measures when the 2 TX groups were compared. TX rats had significantly more (p=0.0002) histological lesions consistent with CAN and elevation in TNF-α (p=0.0402) compared to CON animals.
Conclusions and clinical relevance: In this study, spironolactone did not protect against the development or progression of CAN.
Impact for human medicine: The impact of aldosterone on the occurrence of CAN in humans following renal transplantation remains an area of investigation.

When senior leadership endorses quality improvement priorities, their staff is more likely to comply. To honor Centers for Medicare and Medicaid Services’s (CMS) mandates, dialysis clinic managers must ensure that transplant education takes place within their centers. We surveyed 131 dialysis clinic managers in End Stage Renal Disease (ESRD) Network 12 (the Heartland Kidney Network) to understand their transplant attitudes, knowledge, active educational programs, and perceived barriers to transplant. Few reported that there was a designated transplant educator (40%) or formal transplant education program (33%) available at their dialysis centers. Transplant education most commonly occurring with all patients included educators (53%) or physicians (49%) discussing transplant with the patient, giving them handouts or brochures (40%), the transplant center phone numbers (36%), and referring them to other transplant educational resources (22%). Over half were dissatisfied with transplant education available (56%) and felt that their educators did not have sufficient time to educate (57%). Most did not know that a kidney transplant from a living donor is expected to last 15-20 years (78% incorrect) or that almost 90% of kidneys function for at least one year (71% incorrect). Managers with formal transplant education programs in their dialysis centers were more likely to report that their patients were talking to educators (80% vs. 49%, χ2=11.13, p<.01) and given handouts or brochures about transplant (67% vs. 33%, χ2=14.63, p<.01). Unless dialysis corporations implement specific transplant education policies and procedures, transplant centers support these initiatives, and CMS ensures compliance, transplant education within dialysis centers will be intermittent.

We report the case of a 49-year-old renal and pancreatic female transplant recipient, who presented a drug interaction between tacrolimus, warfarin and pristinamycin. Three days after oral pristinamycin 1000 mg bid administrations, the patient presented nausea, vomiting, abdominal pain and violent headaches that required hospitalization. Tacrolimus trough level was 5 times higher (34.9 μg/l) than the target required (5-8 μg/l) and the INR was at 5.8 (therapeutic index between 2 and 3) despite a stable kidney function (serum creatinine 130 μmol/L) and no other organic disorders. Five days following discontinuation, drug monitoring revealed adequate tacrolimus plasma trough concentrations (8.9 μg/l) and the INR subsequently decreased.

Pristinamycin is an antibiotic effective against the majority of Gram positive bacteria. This drug is an inhibitor of the multidrug transporter P-glycoprotein (P-gp) that could lead to the accumulation of tacrolimus. Moreover, pristinamycin IIA is the active metabolite of quinupristin/dalfopristin which, is known to be an inhibitor of cytochrome P450 3A4 (CYP 3A4). Our case supposes that pristinamycin is also an inhibitor of CYP 3A4 that can lead to an increase of tacrolimus levels.

This case report brings to light potential drug interactions of pristinamycin with narrow therapeutic index drugs such as tacrolimus and warfarin.